A Study on Potential Phytopharmaceuticals Assets in Catharanthus Roseus L

Home , Apocynaceae, Catharanthus, Catharanthus roseus, Teucrium chamaedrys

International Journal of Life Sciences Biotechnology and Pharma Research Vol. 5, No. 1, June 2016

A Study on Potential Phytopharmaceuticals Assets in Catharanthus roseus L. (Alba)

Priyanka Tolambiya and Sujata Mathur Department of Botany, University of Rajasthan, Jaipur, India Email: [email protected]

Abstract— Herbal medicinal plants are boon for human catharanthus comes from the Greek for "pure flower" and being as treatment of existing and new diseases are being roseus means red, rose, rosy. It rejoices in sun or rain, or developed either direct or indirect usage of plants. But the seaside, in good or indifferent soil and often grows availability of such plants and their properties also play an wild. It is known as 'Sadabahar' meaning 'always in important role. Catharanthus roseus is a very important bloom' and is used for worship. These are perennial herbs medicinal herb in this direction as availability and its property both are fortunate thing for humankind. This (small shrub) with oppositely decussate or almost plant is used in treatment of several diseases like diabetes, oppositely arranged leaves. Flowers are usually solitary cancer, high blood pressure, asthma, inflammation, in the leaf axils. Each has a calyx with five long, narrow dysentery, brain imbalance, angiogenesis, malaria and other lobes and a corolla with a tubular throat and five lobes. It diseases that occur due to potent micro organisms. Though grows to 20-80 cm high and blooms with pink, purple, or it's a native of Madagascar but it is found most parts of the white flowers [3]. There are over 100 cultivars of C. world. It is also appreciated for its long flowering period roseus known [4]. throughout the year. Its roots, leaves, stems and flowers The main active constituents in plants are phenolic having active constituents to inhibit the growth of disease acids, flavonoids and alkaloids. These active substances and other micro organism. Extracts from the dried or wet flowers and leaves of plants are applied as a paste on perform a number of protective functions in the human wounds in some rural communities. The substances organism and are involved in important anti-oxidative, vinblastine and vincristine extracted from the plant are used anti-allergic, antibiotic, hypoglycaemic and anti- in the treatment of leukemia and Hodgkin's lymphoma. The carcinogen activities [5]-[7]. Catharanthus roseus is fresh juice from the flowers of C. roseus is used to treat formerly known as Vinca rosea and main source of vinca various skin problems e.g. dermatitis, eczema and acne. alkaloids, now sometimes called catharanthus alkaloids. Therefore, the main active constituents present in this plant These are more than 130 alkaloids [8] including about are alkaloids, flavonoids, steroids and phenolic acid. As C. 100 monoterpenoid indole alkaloids [9]. Vinblastine and roseus has mammoth potential to heal many syndrome due vincristine are the dimers, formed by the coupling of to its phytopharmaceuticals assets and it's intact fractions i.e. root, leaf, stem and flower are drug compliant. Still Monoindole alkaloids such as catharanthine and further research is required to find main utility in healing of vindoline[10] mainly present in aerial part of plants used diseases arises due to deadly viruses. to treat cancer. Vincristine and vinblastine require both aerial and root parts of a plant to be synthesized [11]. Index Terms—medicinal plants, Catharanthus roseus, Catharanthus roseus as a source of valuable alkaloids alkaloids, anti-diabetic, anti-oxidant, anti-fungal, anti- resembling those from Rauwolfia species. Roots of bacterial. Catharanthus have more ajmalicine (vasodilating) and serpentine (hypertensive) than even Rauwolfia serpentina. I. INTRODUCTION They also possess reserpine[12], [13]. The alkaloids Catharanthus roseus, commonly known as the possess hypotensive, sedative and transquillising Madagascar periwinkle, is a species of apocynaceae properties. The root bark contains the alkaloid Alstonine family and endemic to Madagascar. Other English names which has been used traditionally for its calming effect occasionally used include Vinca rosea, Lochnera rosea, and its ability to reduce blood pressure. Yohimbine Ammocallis rosea, Cape periwinkle, rose periwinkle, rosy (Procomil) is an alkaloid with stimulant and aphrodisiac periwinkle and "old-maid". effects found naturally in Pausinystalia yohimbine [14]. C. Catharanthus is a genus of flowering plants in the roseus also shows the presence of this compound along dogbane family, Apocynaceae. Like genus Vinca, they with another flavonoid hirsutidin [15]. Prepare decoction are known commonly as periwinkles. There are eight of C. roseus leaves and drink early in the morning for 7 known species. Out of eight, seven are endemic to days its beneficial to diabetes patients. Madagascar [1]. Though one, C. roseus, is widely Catharanthus roseus contains significant amounts of naturalized around the world [2]. The eighth species, C. volatile and phenolic compounds including pusillus is native to India and Sri Lanka. The name caffeoylquinic acids and flavonal glycosides which are known to antioxidant activity. It has a important role in the body defense system that is acts as a antioxidants Manuscript received December 21, 2015; revised June 1, 2016.

against reactive oxygen species (ROS) [16]. B. Classification Catharanthus roseus also possess good antibacterial, antifungal, anti-oxidant, anti-diabetic and antiviral Kingdom Plantae potential [13], [17], [18]. Phylum Magnoliopsida

II. TAXONOMY Class Annonidae

Order Gentianales A. Description

Family Apocynaceae Catharanthus roseus is a long-lived (perennial) sub- shrub or herb, usually erect, 30-100 cm high and at least Genus Catharanthus somewhat woody at the base, sometimes sprawling. Species roseus White latex is present. Botanical Name Catharanthus roseus Stems are cylindrical (terete), longitudinally ridged or narrowly winged, green or dark red, pubescent at least when young. Leaves opposite, borne on short petioles, C. Vernacular names 2.5-9.0 cm long, usually elliptical to obovate (egg-shaped in outline but with the narrower end at the base), green Common name Periwinkle,Vinca with paler veins. The leaf tip is rounded to acute with a Hindi Sadabahar tiny point extending from the midrib. Stems and leaves usually with hairs (pubescent), sometimes hairless. Malyalam ShayamNaari, Usamalari Marathi Sadaphuli Bengali Nayantara Oriya Visayan Punjabi Rattanjot Sanskrit Nityakalyani Tamil Sudukattumallikai Telugu Billaganneru. Kannada Kempukesi, Kanigalu European Vinca branca Spanish Vinca rosada

There are two major cultivars of Catharanthus roseus L., which are distinguishable on the basis of their flower colors, namely „rosea‟ (Pink) and „alba‟ (White) shown in Fig. 2, are commonly found in India.

Figure 1. 1, flowering twig; 2, flower; 3, base and top of corolla tube in longitudinal section; 4, fruit; 5, seed.(Source: PROSEA)

Flowers borne in leaf axils; either singly or paired on very short stalks (pedicels). Sepals 5, 2-6 mm long, narrow, usually with hairs (pubescent). Corolla with a (a) rosea (b) alba long narrow tube and lobes that spread perpendicular to Figure 2. Major cultivars of Catharanthus roseus the tube and almost flat.; corolla tube greenish, usually at least 2.2 cm long, with the inside of the mouth often dark pink or sometimes yellow, pubescent inside the throat III. PROPERITIES with rings of stiff hairs below the mouth and anthers; corolla lobes 5, pink to white or pinkish A. Alkaloids purple, 1.0-2.8 cm long, obovate. Anthers 5, attached to Catharanthus roseus has been found to contain as the inside of the corolla tube in the upper portion and many as 130 constituents with an indole or dihydroindole concealed within it structure. The principal component is vindoline ( up to The fruit is a follicle, 2.0-4.7 cm long, with numerous 0.5%); other compounds are serpentine, catharanthine, small black seeds. ajmalicine, akuammine, lochnerine, lochnercine and

2 International Journal of Life Sciences Biotechnology and Pharma Research Vol. 5, No. 1, June 2016

tetrahydroalstonine. Alkaloids present in various part of B. Traditional Catharanthus roseus are summarized below: In traditional medicine, Catharanthus roseus has been  Leaf- Catharanthine, Vindoline, Vindolidine, used to treat a variety of ailments in Madagascar as well Vindolicine, Vindolinine, ibogaine, yohimbine, as in other parts of the world where the plant has raubasine, Vinblastine, Vincristine, Leurosine, naturalized. Folk Remedies and Traditional Uses of Lochnerine. Catharanthus roseus are summarized below:  In India, the juice from the leaves is used to treat  Stem- Leurosine, Lochnerine, Catharanthine, . Vindoline. wasp sting with [21]  In Hawai‟i extract of boiled plant is used to arrest  Root- Ajmalacine, Serpentine, Catharanthine, bleeding[21]. Vindoline, Leurosine, Lochnerine, Reserpine,  In Cuba and Jamaica- Flower extract is used for eye Alstonine, Tabersonine, Horhammericine, wash in infants[21]. Lochnericine, echitovenine [19].  In Africa- Leaves are used for menorrhagia and  Flower- Catharanthine, Vindoline, Leurosine, rheumatism. (Dobelis, 1997; Walts, 2004) [21]. Lochnerine, Tricin (Flavones).  In Philippines-Decoction of leaves is used in diabetes  Seeds - Vingramine, Methylvingramine [20]. and decoction of young leaves is used in stomach The physiologically important and antineoplastic cramps, root decoction is used for intestinal alkaloids, vincristine and vinblastine (Fig. 2), are mainly parasitism. Infusion of leaves is used for treating present in the leaves and antihypertensive alkaloids are menorrhagia. Crude leaf extracts and root has anti found in roots such as ajmalicine, serpentine, and cancer activity. Roots used for dysentery [22]. reserpine (2 ref). Vincristine and vinblastine alkaloids are  In Madagascar- The bitter and astringent leaves are used in the treatment of various types of lymphoma and used as vomitive, roots used as purgative, vermifugl, leukemia (3,4 ref). These Catharanthus alkaloids are also depurative, hemostatic and toothache remedies [22]. used for the treatment of both malignant and non-  In Mauritius- The juice of leaves is used for malignant diseases and in platelet and platelet associated indigestion and dyspepsia [22]. disorders.  In West Indies and Nigeria- The plant is used in diabetes [22].  In Bahamas- Decoction of flower is used in asthma, tuberculosis and flatulence [22].  In Malaysia- The plant is used in diabetes, hypertension, insomnia and cancer [22].  In America- Gargle of plant is used to ease soarthroats, chest ailments and laryngitis [22]. C. Modern While researching the anti-diabetic properties of the (a) plant in the 1950s, scientists discovered the presence of several highly toxic alkaloids in its tissues. Figure 3. Structure formulae of vincristine (a) and vinblastine (b) in Catharanthus roseus L. These alkaloids are now used in the treatment of a number of different types of cancer, with one derived compound, called vincristine, having been credited with IV. USES raising the survival rate in childhood leukaemia from less A decoction of all parts of Catharanthus roseus is well than 10% in 1960 to over 90% today. Brief summary of known is well known as an oral hypoglycaemic agent. Catharanthus roseus‟s therapeutic properties are The decoction is also taken to treat presented in Table I.

TABLE I. THERAPEUTIC PROPERTIES CATHARANTHUS ROSEUS S. Therapeutic Plant parts and Doses Organism References No. Properties methods used Anti-diabetic Dichloromethane: methanol extract (1:1) of streptozotocin (STZ) induced 1. 23,24,25 activity leaves and twigs 500mg/kg diabetic rat model.

Anti-oxidant Methanolic leaf extract , Dichloromethane 2. 12.5and 6,26 activity extract (DE), Ethanolic extracts of the roots β-TC6 cells 25.0 µg/mL. Hypolipidemic Leaf juice of Catharanthus roseus, Guinea Pigs, 3. - Activity Aqueous extract of leaves. Alloxan induced diabetic rats. 22,27

Wound Healing Streptozotocin-induced diabetic 4. 200 and 400 Activity Methanolic extract of C. roseus leaf Mice 28,29 mg/kg HCT-116 colorectal carcinoma 5. Cytotoxic activity - Methanolic extract cell 30

3 International Journal of Life Sciences Biotechnology and Pharma Research Vol. 5, No. 1, June 2016

Different extract (acetone, methanol, Aspergillus niger, Antifungal 6. ethanol), - Candida albicans, Penicillium activity 31,32, 33 Ethanol leaf extract chrysogenum Staphyloco ccusaureus, E.coli,

Antibacterial Different extract (acetone, methanol, Klebsiellaoxytoca, Klbsiella 7. - activity ethanol), pneumonia, 31,32,33 Ethanol leaf extract Pesudomonasaerugenosa, Antidiarrheal 200 and 500 8. activity Ethanolic leaf extract mg/kg Wistar rat 17,32 Hypoglycemic Aqueous extract of flowers, leaves, roots, 9. 250 mg/kg Healthy and alloxan diabetic mice activity and stems 34 Anti- 55mg/kg, Streptozotocin-induced diabetic Leaf powder, leaf dichloromethane: 10. hyperglycemic 500 mg/ rats, normal and Alloxan induced methanol (1:1) Extracts 23,27,35, activity body weight diabetic rats. Ethanolic, Methanolic and Aqueous Extract MCF (breast cancer) cell lines, Anticancer 11. of leaves , stem, root, aerial part of 50 and 100 Jurkat, HCT-116, 9KB,P-338 cell 36,37, activity Catharanthus roseus mg/kg lines 38,39 Anti-helminthic Ethanol extract of Catharanthus 12. 16,40 activity roseus(Whole plant) 250 mg/ml Pheretima posthuma vaccinia and polio type III 13. Antiviral activity Selected Catharanthus alkaloids. - 41 viruses.

V. CATHARANTHUS ROSEUS IN DIABETIC TREATMENTS TABLE II. CATHARANTHUS ROSEUS IN DIABETES Diabetes mellitus is disease common in all parts of the Type of Symptoms Plant part used and use method world. The use of insulin and control achieved over the Insulin Disturbances of Aqueous Extracts from disease are of comparatively recent origin when one takes dependent carbohydrate, fat, and Catharanthus roseus Diabetes protein metabolism leaf, stem, root, flower into account the long history of this disease. The problem mellitus resulting from defects in / Whole plant of drug intolerance, hypersensitivity and resistance to insulin secretion, insulin action or both insulin makes it all the more important to search for safe, Non- Insulin resistance Aqueous Extracts from effective and cheaper remedies. Even before the advent of insulin (Gita Bisla et Catharanthus roseus modern medicine, man has been using various forms of dependent al.,2013)[13] leaf Diabetes plant therapy to flight this disease. C. roseus has been mellitus traditionally used for diabetes. Recent studies have shown that C. roseus has significant anti-diabetic activity. VI. CONCLUSION AND FUTURE WORK Leaf extract of C. roseus reportedly lowered blood sugar The leaf juice or water decoction of Catharanthus in STZ-diabetic rats [42]. Hypoglycemic activity has also roseus L. (Apocyanaceae) is used as a folk medicine for been reported for dichloromethane-methanol extract of the treatment of diabetes all over the world. In stems and twigs of the plant in STZ-diabetic rats [24]. continuation to this its other parts like root, leaf, stem & The extract reportedly improved enzymic activities of flower have active components like alkaloid, flavonoids, steroids and phenolic acids which effectively make it in glycogen synthase, glucose 6-phosphate dehydrogenase, usage as antimicrobial, anti diabetic, anti- syndrome, anti- succinate dehydrogenase and malate dehydrogenase in oxidant. The above study reveals that C. roseus has a liver of diabetic animals. Juice of fresh leaves of the plant potential Phytopharmaceuticals assets and further more was observed to reduce blood glucose in normal and research is require to find out its actual responsible alloxan diabetic rabbit [43]. Extract of the plant also component, so that its main utility can be used in healing stimulated glucose utilization in hepatocytes[44]. of diseases arises due to deadly. Ethanolic extract of the plant lowered blood glucose REFERENCES levels in oral glucose tolerance tests in glucose induced hyperglycemic rats [45]. Antihyperglycemic activity has [1] G. Brun, J.M. Bessie`re, M.G. Dijoux-Franca, A.M. David and B. Mariotte,“Volatile Components of Catharanthus roseus (L.) G. been reported following administration of leaf powder in Don (Apocynaceae),”Flavour Fragr. J. vol. 16, no. 2, pp. 116-119, STZ-diabetic rats [46]. Inhibition of aldose reductase (a 2001. [2] S. Rahmatzadeh & S. K. Kazemitabar,“Biochemical and key enzyme in cataractogenesis) as well as free radical antioxidant changes in regenerated periwinkle plantlets due to scavenging activity was reported for the plant extract, mycorrhizal colonization during acclimatization,”.IJACS, vol. 5, no 14, pp.1535-1540, 2013. suggesting that administration of the extract can delay [3] A. Swanberg & W. Dai, “Plant Regeneration of Periwinkle diabetes-induced cataract formation [47]. Also some (Catharanthus roseus) via Organogenesis,”Hort Science. vol.43, studies has shown that C. roseus is effective in both no. 3, pp. 832-836, 2008. [4] C. Ku, W. C. Chung , L. L. Chen, and C. H. Kuo, “The Complete insulin dependent and non-insulin dependent diabetes Plastid Genome Sequence of Madagascar Periwinkle (Table II). Catharanthus roseus (L.) G. Don: Plastid Genome Evolution, Molecular Marker Identification and Phylogenetic Implications in Asterids,”PLOS ONE, vol. 8, no. 6, pp. 1-11,2013.

4 International Journal of Life Sciences Biotechnology and Pharma Research Vol. 5, No. 1, June 2016

[5] S. M. Stanković, M. Topuzović, S. Solujić, and V. Mihailović, induced diabetic rats,” J. Ethnopharmacol., vol. 76, no. 3, pp. 269- “Antioxidant activity and concentration of phenols and flavonoids 77, 2001. in the whole plant and plant parts of Teucrium chamaedrys L. var. [25] S. N. Singh, et al., “Effect of an antidiabetic extract of glanduliferum Haussk,” J. Med. Plant Res., vol. 4, pp. 2092-2098, Catharanthus roseus on enzymic activities in streptozotocin 2010. induced diabetic rats,”Journal of Ethnopharmacolog, vol. 76, pp. [6] S. M. Stanković, G. M. Ćurčić, B. J. Žižić, D. M. Topuzović, R. 269–277, 2007. S .Solujić and D.S. Marković, “Teucrium plant species as natural [26] M. A. Bhutkar and S. B. Bhise, “Comparative Studies on sources of novel anticancer compounds: Antiproliferative, Antioxidant Properties of Catharanthus rosea and Catharanthus proapoptotic and antioxidant properties,”.Int. J. Mol. Sci., vol. 12, alba,” International Journal of Pharm. Tech. Research, vol. 3, no. pp. 4190–4205, 2011. 3, pp. 1551-1556, 2011. [7] S. M. Stanković, N. Nićiforović, V. Mihailović, M. Topuzović, [27] M. Jayanthi, N. Sowbala, G. Rajalakshmi, U. Kanagavalli, and V. and S. Solujić, “Antioxidant activity, total phenolic content and Sivakumar,“Study of Anti- hyperglycemic effect of Catharanthus flavonoid concentrations of different plant parts of Teucrium roseus in Alloxan induced Diabetic Rats,” International Journal of polium L. subsp. Polium,” Acta Soc. Bot. Pol., vol. 81, pp. 117– Pharmacy and Pharmaceutical Sciences. vol. 2, no. 4, pp. 114-116, 122, 2012. 2010. [8] R. Van Der Heijden, D. I. Jacobs, W. Snoeijer, D. Hallard, and R. [28] A. Singh, P. K. Singh, and R. K. Singh, “Antidiabetic and wound Verpoorte, “The Catharanthus alkaloids: pharmacognosy and healing activity of Catharanthus roseus L. in streptozotocin- biotechnology,” Curr. Med. Chem., vol. 11, no. 5, pp. 607-28, induced diabetic mice,” American Journal of Phytomedicine and 2004. Clinical Therapeutics, vol. 2, no. 6, pp. 686-692, 2014. [9] N. Rasool, K. Rızwan, M. Zubaır, K. Naveed, and V. Ahmed, [29] M. Favali, R. Muestti, S. Benvenuti, A. Bianchi, and L. Pressacco, “Antioxidant potential of different extracts and fractions of “Catharanthus roseus L. plants and explants infected with Catharanthus roseus shoots,” International Journal of phytoplasmas: Alkaloid production and structural observations,” Phytomedicine, vol. 3, pp. 108-114, 2011. Protoplasma, vol. 223, no. 1, pp. 45-51, 2014. [10] K. Meenakshi , S. L Neha., C. amesh, and C. Sheela, [30] M. Siddiqui, Z. Ismail, A. Aisha, and A. Majid, “Cytotoxic “Catharanthus roseus and prospects of its endophytes : A New activity of Catharanthus roseus (Apocynaceae) crude extracts and avenue for production of bioactive metabolites,” IJPSR. vol. 4, no. pure compounds against human colorectal carcinoma cell line,” 7, pp. 2705-2716, 2013. International Journal of Pharmacology, vol. 6, no. 1, pp. 43-47, [11] V. De Luca, P. Laflamme, “The expanding universe of alkaloid 2010. biosynthesis,” Curr. Opin. Plant Biol., vol. 4, pp. 225–233, 2001. [31] A. Khalil, “Antimicrobial activity of ethanol leaf extracts of [12] P. Mishra , G. C. Uniyal, and S. Sharma, “Pattern of diversity for Catharanthus roseus from Saudi Arabia,” in Proc. of 2nd morphological and alkaloid yield related trades among the International Conference on Environment Science and periwinkle Catharathus roseus accessions collected from in and Biotechnology, 2012. around Indian Subcontinent,” Genetic Research in Crop Evolutio., [32] K. Hassan, A. Brenda, V. Patrick, and O. Patrick, “In vivo vol. 48 , pp. 273-286, 2001. antidiarrheal activity of the ethanolic leaf extract of Catharanthus [13] S Pandey-Rai, et al., “Volatile components of leaves and flowers roseus Linn. (Apocyanaceae) in Wistar rats,” African Journal of of periwinkle Catharanthus roseus (L.) G. Don from New Delhi,” Pharmacy and Pharmacology, vol 5, no. 15, pp. 1797-1800, 2011. Flavour Fragr.,vol. 21,no. 3, pp. 427-430, 2001. [33] S. Balaabirami and S. Patharajan, “In vitro antimicrobial and [14] M .J. Millon, et al., “Agonist and antagonist actions of antifungal activity of Catharanthus roseus leaves extract against Yohimbine as compared to fluparoxan at alpha (2)-adrenergic important pathogenic organisms,” International Journal of receptors (AR),” Synapse, vol. 35, pp. 79-95, 2002. Pharmacy and Pharmaceutical Sciences, vol 4, no. 3, pp. 487-490, [15] A. Piovan and R. Fillipini, “Anthocyanins in Catharanthus roseus 2012. in vivo and in vitro: A review,” Phytochem. Rev., vol. 6, pp. 235- [34] E. Vega-Ávila, J. L. Cano-Velasco, F. J. Alarcón-Aguilar, M. C. 242, 2007. FajardoOrtíz, J. C. Almanza-Pérez, and R. Román-Ramos, [16] K. Kabesh, P. Senthilkumar, R. Ragunathan, and R. Raj Kumar, “Hypoglycemic activity of aqueous extracts from Catharanthus “Phytochemical analysis of Catharanthus roseus Plant Extract and roseus. evidence-based complementary and alternative medicine,” its Antimicrobial Activity,” Int. J. Pure App. Biosci., vol. 3, no. 2, Article ID, 934258,7 pages doi:10.1155/2012/934258, 2012. pp. 162-172, 2015. [35] K. Rasineni, R. Bellamkonda, S. Reddy, and S. Desireddy, [17] S. Gajalakshmi, S. Vijayalakshmi, and R. V. Devi, “Antihyperglycemic activity of Catharanthus roseus leaf powder “Pharmacological activities of Catharanthus roseus: A perspective in streptozotocin-induced diabetic rats,” Pharmacognosy Res., vol. review,” Int. J. Pharma Sci., vol. 4, no. 2, pp. 431-439, 2013. 2, no. 3, pp. 195–201, 2010. [18] A. Marcone , E. Ragozzino, and E. Seemuller, “Dodder [36] N. H. Ahmad, R. A, Rahim, and I. Mat, “Catharanthus roseus transmission of alder yellows phytoplasma to the experimental aqueous extract is cytotoxic to Jurkat leukemic T-cells but induces host Catharanthus roseus (periwinkle),” Forest Pathology, vol. 27, the proliferation of normal peripheral blood mononuclear cells” no. 6, pp. 347-350, 1997. Tropical Life Sciences Research, vol. 21, no. 2, pp. 101-113, 2010. [19] J. V. Shanks, R. Bhadra, J. Morgan, S. Rijhwani, and S. Vani, [37] S. Mukhapadhyay and G. A. Cordell, “Catharanthus alkaloid “Quantification of metabolites in the indole alkaloid pathways of XXXVI isolation of vinca leukoblastine (VLB) and periformyline Catharanthus roseus: implications for metabolic engineering,” from Catharanthus trichophyllus and pericyclivine from Biotechnol Bioeng, vol. 58, pp. 333–338, 1998. Catharanthus roseus,”J. Nat. Prod., vol. 44, pp. 335-339, 1981. [20] A. Jossang, P. Fodor, and B. Bodo, “A new structural class of [38] R. S. Ruskin and S. R. Aruna, “In-vitro and in-vivo antitumor bisindole alkaloids from the seeds of Catharanthus roseus: activity of Catharanthus roseus,” Int. Res J Pharm. App. Sci., vol. vingramine and methylvingramine,” J. Org. Chem., vol. 63, pp. 4, no. 6, pp. 1-4, 2014. 7162-7167, 1998. [39] W. Widowati, T. Mozef, C. Risdian, and Y. Yellinaty, “Anticancer [21] V. De Luca and P. Laflamme, “The expanding universe of and free radical scavenging potency of Catharanthus roseus, alkaloid biosynthesis,”Curr. Opin. Plant Biol., vol. 4, pp. 225–233, Dentrophthoe petandra, Piper betle and Curcuma mangga 2001. extracts in breast cancer cell lines,” Oxid Antioxid Med. Sci., vol. 2, [22] L. Muralidharan, “Catharanthus roseus leaves as an antidiabetic no. 2, pp. 137-140, 2013. and hypolipidemic agents in alloxan- induced diabetic rats,” [40] H. Hoskeri, et al., “In-vitro antihelminthic activity of American Journal of Phytomedicine and Clinical Therapeutics, Catharanthus roseus extract,” International Journal of vol. 2, pp. 1393-1396, 2014. Pharmaceutical Sciences and Drug Research, vol. 3, no. 3, pp. [23] G. Bisla, S. Choudhary, E. Singh, and V. Chaudhary, 211-213, 2011. “Hyperglycemia and hyperlipidemia mitigating impact of [41] N. R. Farnsworth, G. H. Svoboda, and R. N. Blomster, “Antiviral Catharanthus roseus (Sadabahar) leaves aqueous extract on type2 activity of selected Catharanthus alkaloids,” J. Pharmacol. Sci., diabetes mellitus subjects,” Asian Journal of Plant Science and vol. 57, no. 12, pp. 2174–2175. Research. vol. 3, pp. 170-174, 2013. [42] R. R. Chattopadhyay, “A comparative evaluation of some blood [24] S. N. Singh, et al., “Effect of an anti-diabetic extract of sugar lowering agents of plant origin,” Journal of Catharanthus roseus on enzymic activities in streptozotocin Ethnopharmacology, vol. 67, pp. 367–372,1999.

5 International Journal of Life Sciences Biotechnology and Pharma Research Vol. 5, No. 1, June 2016

[43] S. Nammi, M. K. Boini, S. D. Lodagala, and R. S. Behara, “The cordifolia L. and Catharanthus roseus L.,” Pakistan Journal of juice of fresh leaves of Catharanthus roseus Linn. reduces blood Pharmaceutical Sciences, vol, 22, pp. 402–404, 2009. glucose in normal and alloxan diabetic rabbits,” BMC [46] K. Rasineni, R. Bellamkonda, S. R. Singareddy, and S. Desireddy, Complementary and Alternative Medicine, vol. 3, no. 4, pp. 6882- “Antihyperglycemic activity of Catharanthus roseus leaf powder 6884. in streptozotocin-induced diabetic rats,” Pharmacognosy Research, [44] M. V. Venter, et al., “Antidiabetic screening and scoring of 11 vol. 2, pp. 195–201, 2010. plants traditionally used in South Africa,” Journal of [47] R. N. Gacche and N. A. Dhole, “Profile of aldose reductase Ethnopharmacology, vol. 119, pp. 81–86, 2008. inhibition, anti-cataract and free radical scavenging activity of [45] M. A. Islam, et al., “Oral glucose tolerance test (OGTT) in normal selected medicinal plants: an attempt to standardize the botanicals control and glucose induced hyperglycemic rats with Coccinia for amelioration of diabetes complications,” Food and Chemical Toxicology, vol. 49, pp. 1806–1813, 2011.